Blitzima 100 mg Solution

BLITZIMA contains the active substance rituximab. This is a type of protein called a monoclonal antibody. It sticks to the surface of a type of white blood cell called B - lymphocyte. When BLITZIMA sticks to the surface of this cell, it destroys the cell. BLITZIMA may be used for the treatment of several different conditions in adults. Your doctor may prescribe BLITZIMA for the treatment of:

• Non - Hodgkin’s Lymphoma (NHL) This is a disease of the lymph tissue (part of the immune system) that affects B - Lymphocytes. BLITZIMA can be given alone or with other medicines called “chemotherapy”. If the treatment is working, BLITZIMA may be continued for 2 years after completing the initial treatment.
• Chronic lymphocytic leukaemia (CLL) Chronic lymphocytic leukaemia (CLL) is the most common form of adult leukaemia. CLL affects B - lymphocytes, which originate in the bone marrow and develop in the lymph nodes. Patients with CLL have too many abnormal lymphocytes, which accumulate mainly in the bone marrow and blood. The spread of these abnormal B - lymphocytes is the cause of symptoms you may have. BLITZIMA in combination with chemotherapy destroys these cells.
• Rheumatoid arthritis (RA) BLITZIMA is used for the treatment of rheumatoid arthritis. Rheumatoid arthritis is a disease of the joints. B lymphocytes are involved in the cause of some of the symptoms you have. BLITZIMA is used to treat rheumatoid arthritis in people who have already tried some other medicines which have either stopped working or have not worked well enough. BLITZIMA is usually taken together with another medicine called methotrexate. BLITZIMA slows down the damage to your joints caused by rheumatoid arthritis and improves your ability to do normal daily activities.
• Granulomatosis with polyangiitis (GPA) or Microscopic polyangiitis (MPA) BLITZIMA is used for inducing remission in granulomatosis with polyangiitis (formerly called Wegener’s granulomatosis) or microscopic polyangiitis, taken in combination with corticosteroids. Granulomatosis with polyangiitis and microscopic polyangiitis are two forms of inflammation of the blood vessels which mainly affects the lungs and kidneys but may affect other organs as well. B - lymphocytes are involved in the cause of these conditions.
• Pemphigus vulgaris (PV) BLITZIMA is used for the treatment of patients with moderate to severe pemphigus vulgaris (PV). PV is an autoimmune condition that causes painful blisters on the skin and lining of the mouth, nose, throat and genitals.

You should not be administered with BLITZIMA if:

• you are hypersensitive (allergic) to rituximab, other proteins which are like rituximab or any of the other ingredients of BLITZIMA (listed in section 6).
• you have a severe active infection at the moment, infection with tuberculosis (TB), or have recently been in close contact with someone who has a tuberculosis (TB) infection.
• you have a weak immune system.
• you have severe heart failure or severe uncontrolled heart disease and have rheumatoid arthritis, granulomatosis with polyangiitis or microscopic polyangiitis.

Do not use BLITZIMA if any of the above apply to you. If you are not sure, talk to your doctor, pharmacist or nurse before you use BLITZIMA.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before you use BLITZIMA if:

• you have ever been diagnosed with or might currently have a tuberculosis (TB) infection. This is because BLITZIMA could cause the tuberculosis infection to become active again. For this reason, your doctor may test for tuberculosis and indicate that you require preventative treatment for tuberculosis infection before using BLITZIMA. If the test is negative your doctor may monitor and periodically test for TB infection during your treatment with BLITZIMA.
• you are infected with HIV.
• you have ever had or might now have a hepatitis infection. This is because in a few cases, BLITZIMA could cause hepatitis B to become active again, which can be fatal in very rare cases. Patients who have ever had hepatitis B infection will be carefully checked by their doctor for signs of this infection.
• you have ever had heart problems (such as angina, palpitations or heart failure) or breathing problems.
• you are taking treatment for high blood pressure. You may be asked not to take your medicines for 12 hours before your infusion of BLITZIMA. Some people experience a drop in their blood pressure during the infusion.

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist, or nurse before you use BLITZIMA. Your doctor may need to take special care during your treatment with BLITZIMA.

If you have rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis or pemphigus vulgaris also tell your doctor:

• you have taken or are taking medicines such as chemotherapy or immunosuppressive medicines which may affect your immune system.
• if you think you may have an infection, even a mild one like a cold. The cells that are affected by BLITZIMA help to fight infection and you should wait until the infection has passed before you use BLITZIMA. Also tell your doctor if you have had a lot of infections in the past or suffer from severe infections.
• if you think you may need any vaccinations in the near future, including vaccinations for travel to other countries. Some vaccines should not be given at the same time as BLITZIMA or in the months after you receive BLITZIMA. Your doctor will check if you should have any vaccines before you use BLITZIMA.

Children and adolescents

Talk to your doctor, pharmacist or nurse before you are given this medicine if you, or your child, are under 18 years of age. This is because there is not much information about the use of BLITZIMA in children and young people.

Other medicines and BLITZIMA

Always tell your healthcare provider if you are taking any other medicine. (This includes all complementary or traditional medicines.) Tell your doctor or pharmacist if you are currently using:

• if you are taking medicines for high blood pressure. You may be asked not to take these other medicines 12 hours before you are given BLITZIMA. This is because some people have a fall in their blood pressure while they are being given BLITZIMA.
• if you have ever taken medicines which affect your immune system, such as chemotherapy or immune - suppressive medicines.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding your baby, please consult your doctor, pharmacist or other healthcare professional for advice before taking BLITZIMA. You must tell your doctor or nurse if you are pregnant, think that you might be pregnant or are planning to become pregnant. This is because BLITZIMA can transfer across the placenta and may affect your baby. If you can get pregnant, you and your partner must use an effective method of contraception while using BLITZIMA. You must also do this for 12 months after your last treatment with BLITZIMA. Do not breastfeed while you are being treated with BLITZIMA. Also, do not breastfeed for 12 months after your last treatment with BLITZIMA. This is because BLITZIMA may pass into breast milk.

Driving and using machines

BLITZIMA may impair your ability to drive a vehicle or use machines. Take special care before performing tasks requiring your attention, until you know how BLITZIMA will affect you.

BLITZIMA contains sodium BLITZIMA contains 2,3 mmol (or 52,6 mg) sodium per 10 mL vial and 11,5 mmol (or 263,2 mg) sodium per 50 mL vial, equivalent to 2,6 % (for 10 mL vial) and 13, 2 % (for 50 mL vial) of the WHO recommended maximum daily intake of 2 g sodium for an adult. This needs to be taken into consideration by patients on a controlled sodium diet.

Do not share medicines prescribed for you with any other person. Always take BLITZIMA exactly as your doctor has instructed you. You should check with your doctor or pharmacist if you are unsure.

How it is given

BLITZIMA will be given to you by a doctor or nurse who is experienced in the use of this treatment. They will watch you closely while you are being given this medicine. This is in case you get any side effects. You will always be given BLITZIMA as a drip (intravenous infusion).

Medicines given before each BLITZIMA administration

Before you are given BLITZIMA, you will be given other medicines (pre - medication) to prevent or reduce possible side effects.

How much and how often you will receive your treatment

a) If you are being treated for non - Hodgkin’s Lymphoma

• If you are having BLITZIMA alone BLITZIMA will be given to you once a week for 4 weeks. Repeated treatment courses with BLITZIMA are possible.
• If you are having BLITZIMA with chemotherapy BLITZIMA will be given to you on the same day as your chemotherapy. This is usually given every 3 weeks up to 8 times. If you respond well to treatment, you may be given BLITZIMA every 2 or 3 months for two years. Your doctor may change this, depending on how you respond to the medicine.

b) If you are being treated for chronic lymphocytic leukaemia

When you are treated with BLITZIMA in combination with chemotherapy, you will receive BLITZIMA every 28 days until you have received 6 doses. The chemotherapy should be given after the BLITZIMA infusion. Your doctor will decide if you should receive other treatment at the same time.

c) If you are being treated for rheumatoid arthritis

Each course of treatment is made up of two separate infusions which are given 2 weeks apart. Repeated courses of treatment with BLITZIMA are possible. Depending on the signs and symptoms of your disease, your doctor will decide when you should receive more BLITZIMA. This may be months from the previous dose.

d) If you are being treated for granulomatosis with polyangiitis or microscopic polyangiitis

Treatment with BLITZIMA uses four separate infusions given at weekly intervals. A corticosteroid medicine will usually be given by injection before the start of BLITZIMA treatment. Corticosteroid medicine given by mouth may be started at any time by your doctor to treat your condition.

e) If you are being treated for Pemphigus vulgaris (PV)

Each course of treatment is made up of two separate infusions which are given 2 weeks apart. If you respond well to the treatment, you may be given BLITZIMA as a maintenance treatment. This will be administered 1 year and 18 months after the initial treatment and then every 6 months as needed or your doctor may change this, depending on how you respond to the medicine.

If you receive more BLITZIMA than you should Since BLITZIMA is administered by your doctor or nurse, it is unlikely that you will be given too much. There are no known side effects of receiving too much BLITZIMA.

If you forget or miss your BLITZIMA infusion If you forget or miss an appointment to receive BLITZIMA, make another appointment as soon as possible.

BLITZIMA can have side effects. Not all side effects reported for BLITZIMA are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking BLITZIMA, please consult your doctor, pharmacist or other healthcare professional for advice.

Infusion reactions

During or within the first 2 hours of the first infusion you may develop fever, chills and shivering. Less frequently, some patients may get pain at the infusion site, blisters, itching, sickness, tiredness, headache, breathing difficulties, tongue or throat swelling, itchy or runny nose, vomiting, flushing or palpitations, heart attack or low number of platelets. If you have heart disease or angina, these infusion reactions might get worse. Tell the person giving you the infusion immediately if you develop any of these symptoms, as the infusion may need to be slowed down or stopped. You may require additional treatment such as an antihistamine or paracetamol. When these symptoms go away, or improve, the infusion can be continued. These reactions are less likely to happen after the second infusion. Your doctor may decide to stop your BLITZIMA treatment if these reactions are serious.

Infections

Tell your doctor immediately if you get signs of an infection including:

• fever, cough, sore throat, burning pain when passing urine or feeling weak or generally unwell
• memory loss, trouble thinking, difficulty walking or sight loss – these may be due to a very rare, serious brain infection, which has been fatal (progressive multifocal leukoencephalopathy or PML)

You might get infections more easily during your treatment with BLITZIMA. These are often colds, but there have been cases of pneumonia or urinary infections. If you are being treated for rheumatoid arthritis, granulomatosis with polyangiitis or microscopic polyangiitis, you will also find this information in the Patient Alert Card you have been given by your doctor. It is important that you keep this Alert Card and show it to your partner or caregiver.

Skin reactions

Very rarely, severe blistering skin conditions that can be life-threatening may occur. Redness, often associated with blisters, may appear on the skin or on mucous membranes, such as inside the mouth, the genital areas or the eyelids, and fever may be present. Tell your doctor immediately if you have any of these symptoms.

Tell your doctor as soon as possible if you notice any of the following:

a) If you are being treated for non - Hodgkin’s Lymphoma or chronic lymphocytic leukaemia

• Very common side effects (may affect more than 1 in 10 people):
• bacterial or viral infections, bronchitis
• low number of white blood cells sometimes with fever, or low number of blood cells called “platelets”
• feeling sick (nausea)
• bald spots on the scalp, chills, headache
• lower immunity – because of lower levels of anti - bodies called “immunoglobulins” (IgG) in the blood which help protect against infection

Common side effects (may affect up to 1 in 10 people):

• infections of the blood (sepsis), pneumonia, shingles, cold, bronchial tube infections, fungal infections, infections of unknown origin, sinus inflammation, hepatitis B
• low number of red blood cells (anaemia), low number of all blood cells
• allergic reactions (hypersensitivity)
• high blood sugar level, weight loss, swelling in the face and body, high levels of the enzyme LDH in the blood, low calcium levels in the blood
• unusual feelings of the skin – such as numbness, tingling, pricking, burning, a creeping skin feeling, reduced sense of touch
• feeling restless, problems falling asleep,
• becoming very red in the face and other areas of the skin as a consequence of dilation of the blood vessels
• feeling dizzy or anxious
• producing more tears, tear duct problems, inflamed eye (conjunctivitis)
• ringing sound in the ears, ear pain
• heart problems – such as heart attack and uneven or fast heart rate
• high or low blood pressure (low blood pressure especially when standing upright)
• tightening of the muscles in the airways which causes wheezing (bronchospasm), inflammation, irritation in the lungs, throat or sinuses, being short of breath, runny nose
• being sick (vomiting), diarrhoea, pain in the stomach, irritation or ulcers in the throat and mouth, problems swallowing, constipation, indigestion
• eating disorders: not eating enough, leading to weight loss
• hives, increased sweating, night sweats
• muscle problems – such as tight muscles, joint or muscle pain, back and neck pain
• general discomfort or feeling uneasy or tired, shaking, signs of flu
• multiple - organ failure.

Uncommon side effects (may affect up to 1 in 100 people):

• blood clotting problems, decrease of red blood cell production and increase of red blood cell destruction (aplastic haemolytic anaemia), swollen or enlarged lymph nodes
• low mood and loss of interest or enjoyment in doing things, feeling nervous
• taste problems – such as changes in the way things taste
• heart problems – such as reduced heart rate or chest pain (angina)
• asthma, too little oxygen reaching the body organs
• swelling of the stomach

Very rare side effects (may affect up to 1 in 10 000 people):

• short term increase in the amount of some types of antibodies in the blood (called immunoglobulins – IgM), chemical disturbances in the blood caused by break - down of dying cancer cells
• nerve damage in arms and legs, paralysed face
• heart failure
• inflammation of blood vessels including those leading to skin symptoms
• respiratory failure
• damage to the intestinal wall (perforation)
• severe skin problems causing blisters that can be life - threatening. Redness, often associated with blisters, may appear on the skin or on mucous membranes, such as inside the mouth, the genital areas or the eyelids, and fever may be present
• kidney failure
• severe vision loss

Frequency not known:

• a reduction in white blood cells which does not happen straight away
• reduced platelets number just after the infusion – this can be reversed, but can be fatal in rare cases
• hearing loss, loss of other senses

b) If you are being treated for rheumatoid arthritis

Very common side effects (may affect more than 1 in 10 people):

• infections, such as chest infections, urinary tract infections (pain on passing water), colds and herpes infections
• allergic reactions that are most likely to occur during an infusion, but can occur up to 24 - hours after infusion
• changes in blood pressure, nausea, rash, fever, feeling itchy, runny or blocked nose and sneezing, shaking, rapid heart beat, and tiredness
• headache
• changes in laboratory tests carried out by your doctor. These include a decrease in the amount of some specific proteins in the blood (immunoglobulins) which help protect against infection.

Common side effects (may affect up to 1 in 10 people):

• infections such as bronchial tube inflammation (bronchitis)
• a feeling of fullness or a throbbing pain behind the nose, cheeks and eyes (sinusitis)
• fungal foot infection (athlete’s foot)
• high cholesterol levels in the blood
• abnormal sensations of the skin, such as numbness, tingling, pricking or burning, sciatica, migraine, dizziness
• loss of hair
• anxiety
• depression
• indigestion, diarrhoea, acid reflux, irritation and /or ulceration of the throat and the mouth
• pain in the tummy, back, muscles and/or joints.

Uncommon side effects (may affect up to 1 in 100 people):

• excess fluid retention in the face and body
• inflammation, irritation and / or tightness of the lungs, and throat, coughing
• skin reactions including hives, itching and rash
• allergic reactions including wheezing or shortness of breath, swelling of the face and tongue, collapse

Very rare side effects (may affect up to 1 in 10,000 people):

• a complex of symptoms occurring within a few weeks of an infusion of BLITZIMA including allergic like reactions such as rash, itching, joint pain, swollen lymph glands and fever
• severe blistering skin conditions that can be life - threatening. Redness, often associated with blisters, may appear on the skin or on mucous membranes, such as inside the mouth, the genital areas or the eyelids, and fever may be present.
• recurrence of a previous Hepatitis B infection

Frequency not known:

• serious viral infection

Other rarely reported side effects due to BLITZIMA include fewer white cells in the blood (neutrophils) that help to fight against infection. Some infections may be severe (see information on Infections above).

c) If you are being treated for granulomatosis with polyangiitis or microscopic polyangiitis

Very common side effects (may affect more than 1 in 10 people):

• infections, such as chest infections, urinary tract infections (pain on passing water), colds and herpes infections
• allergic reactions that are most likely to occur during an infusion, but can occur up to 24 - hours after infusion
• diarrhoea
• coughing or shortness of breath
• nose bleeds
• raised blood pressure
• painful joints or back
• muscle twitches or shakiness
• feeling dizzy
• tremors (shakiness, often in the hands)
• difficulty sleeping (insomnia)
• swelling of the hands or ankles

Common side effects (may affect up to 1 in 10 people):

• indigestion
• constipation
• skin rashes, including acne or spots
• flushing or redness of the skin
• blocked nose
• tight or painful muscles
• pain in the muscles or in the hands or feet
• low number of red blood cells (anaemia)
• low numbers of platelets in the blood
• an increase in the amount of potassium in the blood
• changes in the rhythm of the heart, or the heart beating faster than normal

Very rare side effects (may affect up to 1 in 10 000 people):

• severe blistering skin conditions that can be life - threatening. Redness, often associated with blisters, may appear on the skin or on mucous membranes, such as inside the mouth, the genital areas or the eyelids, and fever may be present.
• recurrence of a previous Hepatitis B infection

d) If you are being treated for pemphigus vulgaris

Very common side effects (may affect more than 1 in 10 people):

• allergic reactions that are most likely to occur during an infusion, but can occur up to 24 hours after infusion
• headache
• infections such as chest infections
• long lasting depression
• loss of hair

Common side effects (may affect up to 1 in 10 people):

• infections such as common cold, herpes infections, eye infection, oral thrush and urinary tract infections (pain on passing urine)
• mood disorders such as irritability and depression
• skin disorders such as itching, hives, and benign lumps
• feeling tired or dizzy
• fever
• painful joints or back
• pain in the tummy
• pain in the muscles
• heart beating faster than normal

Frequency not known (frequency cannot be estimated from the available data):

• serious viral infection

BLITZIMA may also cause changes in laboratory tests carried out by your doctor.

Storage of unopened vials

• Store vials in a refrigerator between at 2 °C to 8 °C.
• Keep the vial in the outer carton in order to protect from light.

Storage of diluted product

• The prepared infusion solution of rituximab is physically and chemically stable for 24 hours at 2 °C to 8 °C and subsequently 12 hours at room temperature (not more than 30 °C).
• From a microbiological point of view, the prepared infusion solution should be used immediately. If not used immediately, in - use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 °C to 8 °C, unless dilution has taken place in controlled and validated aseptic conditions.

• STORE ALL MEDICINES OUT OF REACH OF CHILDREN.

• Do not use after the expiry date printed on the carton.

• Return all unused medicine to your pharmacist.

• Do not dispose of unused medicine in drains and sewerage systems (e.g. toilets).